PIAS2_RAT
ID PIAS2_RAT Reviewed; 572 AA.
AC Q6AZ28; Q9Z177;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=E3 SUMO-protein ligase PIAS2;
DE EC=2.3.2.-;
DE AltName: Full=Androgen receptor-interacting protein 3;
DE Short=ARIP3;
DE AltName: Full=DAB2-interacting protein;
DE Short=DIP;
DE AltName: Full=E3 SUMO-protein transferase PIAS2 {ECO:0000305};
DE AltName: Full=Msx-interacting-zinc finger protein;
DE AltName: Full=Protein inhibitor of activated STAT x;
DE AltName: Full=Protein inhibitor of activated STAT2;
GN Name=Pias2; Synonyms=Miz1, Piasx;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH AR, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=9920921; DOI=10.1074/jbc.274.6.3700;
RA Moilanen A.-M., Karvonen U., Poukka H., Yan W., Toppari J., Jaenne O.A.,
RA Palvimo J.J.;
RT "A testis-specific androgen receptor coregulator that belongs to a novel
RT family of nuclear proteins.";
RL J. Biol. Chem. 274:3700-3704(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP INTERACTION WITH AR; ESR1; ESR2; NR3C1 AND PGR.
RX PubMed=11117529; DOI=10.1210/mend.14.12.0569;
RA Kotaja N., Aittomaeki S., Silvennoinen O., Palvimo J.J., Jaenne O.A.;
RT "ARIP3 (androgen receptor-interacting protein 3) and other PIAS (protein
RT inhibitor of activated STAT) proteins differ in their ability to modulate
RT steroid receptor-dependent transcriptional activation.";
RL Mol. Endocrinol. 14:1986-2000(2000).
RN [4]
RP INTERACTION WITH NCOA2, AND MUTAGENESIS OF LEU-23; LEU-304; CYS-385 AND
RP CYS-388.
RX PubMed=11893729; DOI=10.1074/jbc.m106354200;
RA Kotaja N., Vihinen M., Palvimo J.J., Jaenne O.A.;
RT "Androgen receptor-interacting protein 3 and other PIAS proteins cooperate
RT with glucocorticoid receptor-interacting protein 1 in steroid receptor-
RT dependent signaling.";
RL J. Biol. Chem. 277:17781-17788(2002).
RN [5]
RP INTERACTION WITH SUMO1; UBE2I AND AR, SUMOYLATION OF AR; JUN AND NCOA2,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-324; LYS-326; LYS-379;
RP LYS-380; TRP-383; LYS-390; LYS-391; LYS-430 AND LYS-431.
RX PubMed=12077349; DOI=10.1128/mcb.22.14.5222-5234.2002;
RA Kotaja N., Karvonen U., Jaenne O.A., Palvimo J.J.;
RT "PIAS proteins modulate transcription factors by functioning as SUMO-1
RT ligases.";
RL Mol. Cell. Biol. 22:5222-5234(2002).
RN [6]
RP STAT1 SUMOYLATION.
RX PubMed=12855578; DOI=10.1182/blood-2002-12-3816;
RA Ungureanu D., Vanhatupa S., Kotaja N., Yang J., Aittomaeki S., Jaenne O.A.,
RA Palvimo J.J., Silvennoinen O.;
RT "PIAS proteins promote SUMO-1 conjugation to STAT1.";
RL Blood 102:3311-3313(2003).
CC -!- FUNCTION: Functions as an E3-type small ubiquitin-like modifier (SUMO)
CC ligase, stabilizing the interaction between UBE2I and the substrate,
CC and as a SUMO-tethering factor. Plays a crucial role as a
CC transcriptional coregulation in various cellular pathways, including
CC the STAT pathway, the p53 pathway and the steroid hormone signaling
CC pathway. The effects of this transcriptional coregulation,
CC transactivation or silencing may vary depending upon the biological
CC context and PIAS2 isoform studied. However, it seems to be mostly
CC involved in gene silencing. Binds to sumoylated ELK1 and enhances its
CC transcriptional activity by preventing recruitment of HDAC2 by ELK1,
CC thus reversing SUMO-mediated repression of ELK1 transactivation
CC activity (By similarity). Sumoylates PML at'Lys-65' and 'Lys-160' (By
CC similarity). {ECO:0000250}.
CC -!- PATHWAY: Protein modification; protein sumoylation.
CC -!- SUBUNIT: Binds SUMO1 and UBE2I. Interacts with AXIN1, JUN, MDM2, PARK7,
CC TP53 and TP73 isoform alpha, but not TP73 isoform beta. Interacts with
CC STAT4 following IL12 and IFN-alpha stimulation of T-cells. Interacts
CC also with GTF2I, GTF2IRD1, IKFZ1, DAB2 and MSX2, as well as with
CC several steroid receptors, including ESR1, ESR2, NR3C1, PGR, AR, and
CC with NCOA2. Sumoylation of a target protein seems to enhance the
CC interaction. Binds to sumoylated ELK1. Binds DNA, such as CDKN1A
CC promoter, in a sequence-specific manner. Interacts with PLAG1.
CC Interacts with KLF8; the interaction results in SUMO ligation and
CC repression of KLF8 transcriptional activity and of its cell cycle
CC progression into G(1) phase (By similarity). Interacts with IFIH1/MDA5
CC (By similarity). Interacts with PML (By similarity). Interacts with
CC PRDM1 (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:O75928}.
CC -!- SUBCELLULAR LOCATION: Nucleus speckle {ECO:0000269|PubMed:12077349,
CC ECO:0000269|PubMed:9920921}. Nucleus, PML body
CC {ECO:0000250|UniProtKB:O75928}. Nucleus {ECO:0000269|PubMed:9920921}.
CC Note=Colocalizes at least partially with promyelocytic leukemia nuclear
CC bodies (PML NBs) (By similarity). Colocalizes with SUMO1 in nuclear
CC granules (PubMed:12077349). {ECO:0000250|UniProtKB:O75928,
CC ECO:0000269|PubMed:12077349}.
CC -!- TISSUE SPECIFICITY: Mainly expressed in testis.
CC {ECO:0000269|PubMed:9920921}.
CC -!- DEVELOPMENTAL STAGE: Expressed in spermatogonia and in primary
CC spermatocytes up to late pachytene stage (at protein level).
CC -!- DOMAIN: The LXXLL motif is a transcriptional coregulator signature.
CC -!- PTM: Sumoylated. {ECO:0000269|PubMed:12077349}.
CC -!- SIMILARITY: Belongs to the PIAS family. {ECO:0000305}.
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DR EMBL; AF044058; AAD13349.1; -; mRNA.
DR EMBL; BC078775; AAH78775.1; -; mRNA.
DR RefSeq; NP_445789.1; NM_053337.1.
DR AlphaFoldDB; Q6AZ28; -.
DR SMR; Q6AZ28; -.
DR BioGRID; 249702; 3.
DR STRING; 10116.ENSRNOP00000023886; -.
DR iPTMnet; Q6AZ28; -.
DR PhosphoSitePlus; Q6AZ28; -.
DR PaxDb; Q6AZ28; -.
DR PRIDE; Q6AZ28; -.
DR GeneID; 83422; -.
DR KEGG; rno:83422; -.
DR CTD; 9063; -.
DR RGD; 71056; Pias2.
DR eggNOG; KOG2169; Eukaryota.
DR InParanoid; Q6AZ28; -.
DR OrthoDB; 1205949at2759; -.
DR PhylomeDB; Q6AZ28; -.
DR Reactome; R-RNO-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-RNO-3232118; SUMOylation of transcription factors.
DR Reactome; R-RNO-3232142; SUMOylation of ubiquitinylation proteins.
DR Reactome; R-RNO-3899300; SUMOylation of transcription cofactors.
DR Reactome; R-RNO-4090294; SUMOylation of intracellular receptors.
DR Reactome; R-RNO-4551638; SUMOylation of chromatin organization proteins.
DR UniPathway; UPA00886; -.
DR PRO; PR:Q6AZ28; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0050681; F:nuclear androgen receptor binding; IPI:RGD.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; IPI:RGD.
DR GO; GO:0035259; F:nuclear glucocorticoid receptor binding; IPI:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0061665; F:SUMO ligase activity; ISO:RGD.
DR GO; GO:0019789; F:SUMO transferase activity; ISO:RGD.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0030521; P:androgen receptor signaling pathway; IMP:RGD.
DR GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; ISO:RGD.
DR GO; GO:0050775; P:positive regulation of dendrite morphogenesis; IMP:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:RGD.
DR GO; GO:0016925; P:protein sumoylation; ISS:UniProtKB.
DR GO; GO:0060765; P:regulation of androgen receptor signaling pathway; IDA:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0033574; P:response to testosterone; IEP:RGD.
DR GO; GO:0007283; P:spermatogenesis; IEP:RGD.
DR GO; GO:0006351; P:transcription, DNA-templated; ISO:RGD.
DR Gene3D; 1.10.720.30; -; 1.
DR Gene3D; 2.60.120.780; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR027228; PIAS2.
DR InterPro; IPR023321; PINIT.
DR InterPro; IPR038654; PINIT_sf.
DR InterPro; IPR003034; SAP_dom.
DR InterPro; IPR036361; SAP_dom_sf.
DR InterPro; IPR004181; Znf_MIZ.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR10782:SF12; PTHR10782:SF12; 1.
DR Pfam; PF14324; PINIT; 1.
DR Pfam; PF02891; zf-MIZ; 1.
DR SMART; SM00513; SAP; 1.
DR SUPFAM; SSF68906; SSF68906; 1.
DR PROSITE; PS51466; PINIT; 1.
DR PROSITE; PS50800; SAP; 1.
DR PROSITE; PS51044; ZF_SP_RING; 1.
PE 1: Evidence at protein level;
KW DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation; Transferase;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..572
FT /note="E3 SUMO-protein ligase PIAS2"
FT /id="PRO_0000218978"
FT DOMAIN 11..45
FT /note="SAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00186"
FT DOMAIN 134..299
FT /note="PINIT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00799"
FT ZN_FING 331..412
FT /note="SP-RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT REGION 467..473
FT /note="SUMO1-binding"
FT /evidence="ECO:0000250"
FT REGION 523..572
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 19..23
FT /note="LXXLL motif"
FT MOTIF 484..492
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 535..572
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 362
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT BINDING 364
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT BINDING 385
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT BINDING 388
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT MOD_RES 476
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75928"
FT MOD_RES 477
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75928"
FT MOD_RES 478
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75928"
FT MOD_RES 499
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8C5D8"
FT CROSSLNK 46
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O75928"
FT CROSSLNK 249
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O75928"
FT CROSSLNK 430
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O75928"
FT CROSSLNK 435
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O75928"
FT CROSSLNK 443
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O75928"
FT CROSSLNK 452
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O75928"
FT CROSSLNK 489
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O75928"
FT CROSSLNK 502
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O75928"
FT MUTAGEN 23
FT /note="L->A: Loss of enhancement of AR and NR3C1-dependent
FT transactivation; no effect on interaction with AR and
FT NR3C1; when associated with A-305."
FT /evidence="ECO:0000269|PubMed:11893729"
FT MUTAGEN 304
FT /note="L->A: Loss of enhancement of AR and NR3C1-dependent
FT transactivation; no effect on interaction with AR and
FT NR3C1; when associated with A-23."
FT /evidence="ECO:0000269|PubMed:11893729"
FT MUTAGEN 324
FT /note="K->R: No effect on auto-sumoylation; when associated
FT with R-326."
FT /evidence="ECO:0000269|PubMed:12077349"
FT MUTAGEN 326
FT /note="K->R: No effect on auto-sumoylation; when associated
FT with R-324."
FT /evidence="ECO:0000269|PubMed:12077349"
FT MUTAGEN 379
FT /note="K->R: No effect on auto-sumoylation; when associated
FT with R-380."
FT /evidence="ECO:0000269|PubMed:12077349"
FT MUTAGEN 380
FT /note="K->R: No effect on auto-sumoylation; when associated
FT with R-379."
FT /evidence="ECO:0000269|PubMed:12077349"
FT MUTAGEN 383
FT /note="W->A: Loss of promotion of JUN sumoylation; no loss
FT of interaction with SUMO1 and UBE2I."
FT /evidence="ECO:0000269|PubMed:12077349"
FT MUTAGEN 385
FT /note="C->S: Loss of NCOA2-binding; when associated with S-
FT 388."
FT /evidence="ECO:0000269|PubMed:11893729"
FT MUTAGEN 388
FT /note="C->S: Loss of NCOA2-binding; when associated with S-
FT 385."
FT /evidence="ECO:0000269|PubMed:11893729"
FT MUTAGEN 390
FT /note="K->R: No effect on auto-sumoylation; when associated
FT with R-391."
FT /evidence="ECO:0000269|PubMed:12077349"
FT MUTAGEN 391
FT /note="K->R: No effect on auto-sumoylation; when associated
FT with R-390."
FT /evidence="ECO:0000269|PubMed:12077349"
FT MUTAGEN 430
FT /note="K->R: No effect on auto-sumoylation; when associated
FT with R-431."
FT /evidence="ECO:0000269|PubMed:12077349"
FT MUTAGEN 431
FT /note="K->R: No effect on auto-sumoylation; when associated
FT with R-430."
FT /evidence="ECO:0000269|PubMed:12077349"
FT CONFLICT 50
FT /note="T -> S (in Ref. 1; AAD13349)"
FT /evidence="ECO:0000305"
FT CONFLICT 320
FT /note="R -> K (in Ref. 1; AAD13349)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 572 AA; 63431 MW; E107F8B26403D2FB CRC64;
MADFEELRNM VSSFRVSELQ VLLGFAGRNK SGRKHDLLMR ALHLLKSGCT PAVQIKIREL
YRRRYPRTLE GLSDLSTIKS SVFSLDGSSS PVEPDLAVAG IHSLPSTSIA PHSPSSPVAS
VLLQDTKPTF EMQQPSPPIP PVHPDVQLKT LPFYDVLDVL IKPTSLVQSS IQRFQEKFFI
FALTPQQVRE ICISRDFLPG GRRDYTVQVQ LRLCLAETSC PQEDNYPNSL CIKVNGKLFP
LPGYAPPPKN GIEQKRPGRP LNITSLVRLS SAVPNQISIS WASEIGKNYS MSVYLVRQLT
SAMLLQRLKM KGIRNPDHSR ALIKEKLTAD PDSEIATTSL RVSLMCPLGK MRLTIPCRAV
TCTHLQCFDA ALYLQMNEKK PTWICPVCDK KAAYESLILD GLFMEILNDC SDVDEIKFQE
DGSWCPMRPK KEAMKVTSQP CTKVESSSVF SKPCSVTVAS DASKKKIDVI DLTIESSSDE
EEDPPAKRKC IFMSETQSSP TKGVLMYQPS SVRVPSVTSV DPAAIPPSLT DYSVPFHHTP
VSSMSSDLPG EQRRNDINNE VQLGTSSDTV QQ
